Adherence, internalization, and persistence of Helicobacter pylori in hepatocytes

Adherence, internalization, and persistence of Helicobacter pylori in hepatocytes
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DOI:
10.1007/s10620-007-0164-z
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发表时间:
2008-09-01
影响因子:
3.1
通讯作者:
Graham, David Y.
Graham, David Y.
中科院分区:
医学3区
文献类型:
--
作者:
Ito, Kyoko;Yamaoka, Yoshio;Graham, David Y.

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虽然幽门螺杆菌已被确定在肝脏中,螺杆菌的作用。在人类肝脏疾病仍不清楚。本研究探讨了H. pylori的细胞内化,并可在肝细胞中持续存在。大部分H. pylori(1 × 10(7)集落形成单位)粘附于肝细胞。使用庆大霉素侵袭试验,我们发现大约2%被内化,并在传代后持续2个月以上。电子显微镜证实了细胞内螺杆菌的存在。粘附或内化的H. pylori在肝细胞中的表达显著高于胃上皮细胞(P < 0.05),并且还依赖于cag致病岛(派)、VacA、OipA或BabA状态。透射电镜观察H. pylori转化为肝细胞。H. pylori被β 1-整联蛋白受体、染料木黄酮和细胞松弛素D的抗体抑制(P < 0.05),这与β 1-整联蛋白作为表面受体起作用以及对酪氨酸激酶磷酸化和肌动蛋白聚合的额外要求一致。综上所述,H.幽门螺杆菌在体外粘附和侵入肝细胞,这取决于毒力因子,并在传代培养期间持续存在于肝细胞内。β 1-整联蛋白可能是参与H. pylori转化为肝细胞。
Although Helicobacter pylori have been identified in the liver, the role of Helicobacter sp. in human liver diseases remains unclear. This study explored whether H. pylori were internalized and could persist in hepatocytes. The majority of an inoculum of H. pylori (1 x10(7) colony forming units) adhered to hepatocytes. Using the gentamicin invasion assay we found that approximately 2% were internalized and persisted following passage for more than 2 months. Electron microscopy confirmed the presence of intracellular Helicobacter. The number of adherent or internalized H. pylori was significantly greater with hepatocytes than with gastric epithelial cells (P < 0.05) and was also dependent on cag pathogenicity island (PAI), VacA, OipA, or BabA status. Transmission electron microscopy was used to confirm adherence and invasion of H. pylori into hepatocytes. Internalization of H. pylori was inhibited by antibodies to beta 1-integrin receptors, genistein, and cytochalasin D (P < 0.05) consistent with beta 1-integrin acting as a surface receptor with additional requirements for tyrosine kinase phosphorylation and actin polymerization. In summary, H. pylori both adhered to and invaded into hepatocytes in vitro, depending on the virulent factors, and persisted within hepatocytes during subcultures. beta 1-integrin is likely a receptor involved in internalization of H. pylori into hepatocytes.